Title
Antileishmanial activity of a series of <tex>$N^{2},N^{4}$</tex>-disubstituted quinazoline-2,4-diamines Antileishmanial activity of a series of <tex>$N^{2},N^{4}$</tex>-disubstituted quinazoline-2,4-diamines
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Washington, D.C. ,
Subject
Pharmacology. Therapy
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Volume/pages
57(2014) :12 , p. 5141-5156
ISSN
0022-2623
ISI
000338184100012
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
A series of N-2,N-4-disubstituted quinazoline-2,4-diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg(-1) day(-1) for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N-2,N-4-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.
E-info
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